Electronic nicotine delivery devices (ENDS) are novel products that electronically generate a nicotine- containing vapor that is then inhaled by the user. The most popular ENDS on the market are electronic cigarettes, but different ENDS types and brands are engineered differently. The differences include the physical appearance, the nicotine solvent, nicotine concentration and flavor additives to the solution, the capacity of the cartridge containing the solution, the nature of the heating element, and size and type of battery. Since the majority of ENDS contain nicotine and generate inhalable vapor in a manner similar to cigarette smoking, our overall hypothesis is that ENDS might be an effective nicotine delivery device. The primary goal of this research project is to evaluate the quality and efficacy of various electronic nicotine delivery systems (ENDS). Secondarily, we aim to establish an evidence base for evaluating their potential for nicotine delivery to users. This study will investigate various brands and models of ENDS to measure nicotine levels in refill liquids, cartridges, and vapor. We will also complete laboratory testing to investigate how various engineering characteristics influence nicotine yields inhaled by users of the products. We will conduct short- term clinical studies to assess nicotine delivery to the human body from various types of ENDS, including comparisons with conventional cigarettes. The findings can then inform FDA on developing and implementing standard quality procedures and testing methods for ENDS. Our specific aims are as follows: SPECIFIC AIM 1 - PRODUCT CHARACTERIZATION (LABORATORY): Our first aim is to determine the amounts of nicotine present in various brands and types of ENDS, and nicotine yields in vapors generated from the devices. SPECIFIC AIM 2 - DELIVERED LEVELS OF NICOTINE (CLINICAL): We will conduct pharmacokinetic (PK) studies to determine the levels of nicotine effectively delivered by various types of ENDS into the bloodstream and compare them to levels delivered by conventional cigarettes. We will explore the effects of flavorings added to a nicotine solution on puffing topography and nicotine delivery from ENDS. SPECIFIC AIM 3 - DEVELOP A STANDARDIZED TESTING PROTOCOL FOR ENDS THAT WILL REFLECT USERS' PUFFING BEHAVIOR AND PRODUCT CHARACTERISTICS (TRANSLATIONAL): We will develop a standardized testing protocol for various types of ENDS.